Brightline-1: A study to compare brigimadlin (BI 907828) with doxorubicin in people with a type of cancer called dedifferentiated liposarcoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Boehringer Ingelheim International GmbH, Boehringer Ingelheim Espana S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

25 Mar 2022 → 26 Jan 2026

Decision date (initial)

2024-09-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-511361-11-00

EudraCT number

2021-002392-20

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The primary objective of the trial is to evaluate whether brigimadlin is superior to doxorubicin as first line systemic therapy for advanced or metastatic DDLPS.

Secondary objectives 4

1. Phase II part: Select an optimal dose of brigimadlin
2. Phase II part: Evaluate whether the expected benefits of brigimadlin as first line systemic therapy for advanced or metastatic DDLPS outweigh any risks
3. Phase III part: Evaluate whether brigimadlin as first line systemic therapy for advanced or metastatic DDLPS improves the objective response rate, duration of responses, overall survival, disease control rate, tolerability and has a favorable impact on quality of life, compared to doxorubicin.
4. Safety of brigimadlin will be investigated in both parts of the trial.

Conditions and MedDRA coding

Advanced dedifferentiated liposarcoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Provision of signed and dated, written informed consent form ICF in accordance with ICH-GCP and local legislation prior to any trial-specific procedures, sampling, or analyses.
2. Male or female patients ≥18 years old at the time of signature of the ICF. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use 2 medically acceptable methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly beginning at screening, during trial participation, and until 6 months and 12 days after last dose. A list of contraception methods meeting these criteria is provided in the patient information.
3. Histologically proven locally advanced or metastatic, unresectable (surgery morbidity would outweigh potential benefits), progressive or recurrent DDLPS. Locally performed histopathological diagnosis will be accepted for entry into this trial but will be confirmed by independent pathological review while the patients receive treatment in this trial.
4. Written pathology report indicating the diagnosis of DDLPS with positive MDM2 immunohistochemistry or MDM2 amplification as demonstrated by fluorescence in situ hybridization or NGS must be available.
5. Formalin fixed paraffin embedded tumor blocks or slides must be available for retrospective histopathological central review.
6. Presence of at least one measurable target lesion according to RECIST version 1.1. In patients who only have one target lesion, the baseline imaging must be performed at least 2 weeks after any biopsy of the target lesion.
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
8. Patient must be willing to donate blood samples for the pharmacokinetics, pharmacodynamics, and tumor mutation analysis.
9. Further inclusion criteria apply.

Exclusion criteria 9

1. Known mutation in the TP53 gene (screening for TP53 status is not required).
2. Major surgery (major according to the investigator’s assessment) performed within 4 weeks prior to randomization or planned within 6 months after screening.
3. Prior systemic therapy for liposarcoma in any setting (including adjuvant, neoadjuvant, maintenance, palliative).
4. Previous or concomitant malignancies other than DDLPS or WDLPS, treated within the previous 5 years, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ, or other malignancy that is considered cured by local treatment.
5. Previous treatment with anthracyclines in any setting (systemic treatment with other anticancer agents is allowed if completed at least 5 years prior to study entry with the exception of hormone therapy).
6. Patients who must or intend to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
7. Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s) or receiving other investigational treatment(s).
8. Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator’s opinion, makes the patient an unreliable trial participant).
9. Further exclusion criteria apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS). PFS based on central independent review will be assessed at the interim futility analysis at approximately the same time as the end of Phase II, and the primary PFS analysis will take place during the Phase III part.

Secondary endpoints 7

1. Objective response (OR), defined as a best overall response of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1 (based on blinded central independent review) from the date of randomization until disease progression, death, or last evaluable tumor assessment before start of subsequent anti-cancer therapy, loss to follow-up, withdrawal of consent, or end of patient's participation in the trial, whichever occurs first.
2. Duration of objective response (DOR), defined as the time interval from first documented confirmed OR until disease progression or death among patients with confirmed objective response (based on blinded central independent review), whichever occurs first.
3. Overall survival (OS) will be assessed at the end of the Phase III part of the trial. OS is defined as the time interval from randomization until death from any cause.
4. Disease control (DC), defined as a best overall response of CR, PR, or stable disease (SD) according to RECIST version 1.1 (based on blinded central independent review).
5. Health-Related Quality of Life (HRQoL), based on data collected through specific questionnaires (Patient Reported Outcome Measures, PROMs), analyzed from baseline to Week 6 and to Week 18. The HRQoL endpoints are defined as the scores calculated from data collected through selected EORTC QLQ-C30 domains (physical functioning, pain, fatigue, and global health status / quality of life), fatigue and pain based on items from the EORTC QLQ-C30 and the EORTC Item Library, and the EQ-5D5L.
6. Occurrence of treatment-emergent adverse events (AEs).
7. Occurrence of treatment-emergent AEs leading to study drug discontinuation.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Boehringer Ingelheim International GmbH

Sponsor organisation

Boehringer Ingelheim International GmbH

Address

Binger Strasse 173

City

Ingelheim Am Rhein

Postcode

55216

Country

Germany

Scientific contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Public contact point

Organisation

Boehringer Ingelheim International GmbH

Contact name

CT Disclosure & Data Transparency

Boehringer Ingelheim Espana S.A.

Sponsor organisation

Boehringer Ingelheim Espana S.A.

Address

Carrer Prat De La Riba 50, Sant Cugat Del Valles Sant Cugat Del Valles

City

Barcelona

Postcode

08174

Country

Spain

Sponsor responsibilities

Article 77 compliance

Boehringer Ingelheim International GmbH

Contact point sponsor

Boehringer Ingelheim International GmbH

Article 77 implementation

Boehringer Ingelheim International GmbH

Locations

12 EU/EEA countries · 49 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 132 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications